Conservative treatment of breast cancer: a report on 108 patients.

Between 1975 and 1980, 108 breast cancers (T1 and small T2) were treated at the Centre Antoine-Lacassagne (Nice, France) by a combination of conservative surgery and irradiation. Ninety-two of these patients underwent axillary node dissection; 17% of them presented with nodal involvement. All irradiation was given by telecobalt: 45 Gy to the entire breast, 60 Gy to the site of the tumor. All cosmetic results were acceptable. Intramammary recurrences were rare (6%) and independent of the tumor site or size or of any nodal involvement. Solitary metastases (not associated with a local recurrence) were extremely rare (4%) and were observed in patients who had had no nodal involvement. The actuarial survival rate at 5 years is 90%.

Pulmonary toxicity of a combination of low-dose doxorubicin and irradiation for inoperable lung cancer.

In 1980, 27 patients with inoperable lung cancer (26 non-oat cell, one oat cell) were treated by split-course irradiation (40 Gy/10 fractions) plus concomitant low-dose chemotherapy (doxorubicin 10 mg/m2). Twenty-four of the 27 patients received the entire treatment course. Fifteen of the 27 patients were administered various chemotherapy protocols after a period of one month. Median survival was 16 weeks despite a 60% response rate. The lungs were the main site of complications (13 cases of radiation pneumonitis for the 24 patients), which occurred primarily when an objective response was obtained. These complications partially explain the poor results. Injection of doxorubicin during irradiation appears to have been a determining factor.

Plasma levels of 7-hydroxymethotrexate after high-dose methotrexate treatment.

Thirteen patients with cancer being treated with high-dose methotrexate (MTX) chemotherapy (350-5,000 mg/6 h IV were entered in this study. Plasma levels of MTX and 7-OHMTX, its main circulating metabolite, were measured by an HPLC technique. 7-OHMTX appears rapidly in the blood, reaching a maximum 6-12 h after the beginning of treatment. The elimination of 7-OHMTX is slower than that of MTX, but the elimination half-lives (24-48 h) are not significantly different: 25.2 h for 7-OHMTX versus 20.3 h for MTX. In all cases, 24 h after starting infusion plasma levels of 7-OHMTX exceeded those of MTX. There was a positive and significant correlation between the dose administered and peak plasma 7-OHMTX. Finally, 7-OHMTX formation was shown to be relatively stable throughout the treatment.

Relationship between systemic 5-FU passage and response in colorectal cancer patients treated with intrahepatic chemotherapy.

The study described herein was conducted to analyze the relationship between tumor exposure to 5-FU and clinical response. Six patients were placed on continuous 5-day intrahepatic 5-FU chemotherapy for colorectal cancer metastasized to the liver. The starting dose was 600-800 mg/m2 per day; cycles were repeated at 4-week intervals. The 5-FU dose was increased by 250 mg/day at each cycle. All six patients received 3 or more cycles, for a total of 37 cycles. Response was evaluated after each cycle by ultrasonography or computed tomography (CT). Pharmacokinetic data revealed a high individual cycle-to-cycle variability for all six patients in the 5-FU area under the curve (AUC day 1 to day 5) corrected for the dose. These variations in drug biodisposition, reflecting hepatic 5-FU uptake, were significantly related to measurable modifications in the tumor mass in 71% of cycles. The correlation between the reduction in local drug exposure and tumor regrowth was better than that between the increase in local drug exposure and tumor reduction. These findings constitute an original illustration in humans of the experimental concept of the drug exposure/tumor response relationship for 5-FU.

Echographic aspects of thyroid and parotid localizations in non-Hodgkin lymphomas.

The authors present four observations of rare localizations of non-Hodgkin lymphomas (3 cases of lymphoma of the thyroid, 1 case of lymphoma of the parotid), all of which were studied by echography. In two of the thyroid localizations, the echographic pattern was identical to that observed for nodes in non-Hodgkin lymphomas, and thus differs from that of cysts and necrotized or cystic tumors. In the one case of secondary lymphoma of the thyroid, accompanied by diffuse enlargement of the gland but no histological proof, echography revealed only diffuse enlargement, without any anomaly in the echostructure. In the one case of lymphoma of the parotid, the echographic image was similar to that of a lymphomatous node, but it cannot be formally differentiated from the structure which can be observed for a mixed tumor or a cystic lymphangioma.

[Cancer of the prostate: new hormone therapies]. / Cancer de la prostate: nouvelles hormonothérapies.

Beside orchiectomy and estrogens, other endocrine manipulations are proposed for metastatic prostatic cancer patients. Antiandrogens, Cyproterone acetate and Flutamide, are often less efficient but less toxic than DES. Progestational agents medroxyprogesterone acetate, megoestrol acetate, chlormadinone acetate have also a limited activity. Inversely, tamoxifen is very little active. Preliminary results of ketoconazole need more controls. The present aims are to obtain, particularly by hormonal association, a more efficient and less toxic treatment, when DES can be given initially or becomes inefficient.

Value of urinary hydroxyproline and bone isoenzyme of alkaline phosphatase in the early detection and follow-up of bone metastasis in breast cancer patients.

A multiparametric biological study of 178 evaluable breast cancer patients was performed to evaluate the usefulness of individual parameters for the prediction, diagnosis and follow-up of bone metastasis (BM) as compared to physical tests. Serum and urinary calcium and phosphorus were of little discriminative value. The sensitivity and specificity for the urinary hydroxyproline/creatinine ratio (UHP/creat.) were respectively 75% and 81.4% versus 43.2% and 91.4% for the bone isoenzyme of alkaline phosphatase in serum (BIE). During an average follow-up of 14.3 months for 51 patients with bone metastasis, variations in UHP-creat. and BIE correlated with clinical and physical findings; the best correlation was given by UHP/creat. Twenty patients who were initially free of bone metastasis were followed-up for a mean metastasis-free interval of 14 months; UHP/creat. predicted the appearance of bone metastasis in 50% of cases with a lead time of 5.5 months versus 40% and 8.5 months for BIE. Combined use of UHP/creat. and BIE gave a prediction rate of 70% and a mean lead time of 7 months, and this combination of markers thus merits consideration in the management of breast cancer patients.

Systemic blood levels after intra-arterial administration of microencapsulated mitomycin C in cancer patients.

Systemic delivery of mitomycin C (MMC) was studied in 6 patients administered microencapsulated MMC (MMC-mc) by an intra-arterial route (IA): 3 IA liver infusions, 3 IA pelvic infusions. Pharmacokinetic data revealed a lower blood MMC availability (peak plasma levels, AUC 0-4 hours) for the pelvis than for the liver; this was attributed to differences in the blood flow infusion rates at these two sites of administration. Direct comparison of systemic MMC exposure was possible for one patient, who received both IA liver MMC (10 mg in standard form, which served as the control) and IA liver MMC-mc (20 mg the day after). The 65% reduction in MMC-mc bioavailability observed for this patient indicates a quantitative local improvement in exposure to the drug and correlates well with the low incidence of systemic side effects noted in preliminary clinical studies.

[Exploration and surveillance of the retroperitoneal space by lymphography and ultrasonography in patients with non-Hodgkin's lymphomas (author's transl)]. / Exploration et surveillance du rétropéritoine au cours des lymphomes non-hodgkiniens par la lymphographie et l'échographie.

The authors propose to conduct, in a systematic manner, lymphography and ultrasonography examinations before treatment of 75 cases of non-Hodgkin's lymphoma. The latter investigation enables examination of the upper part of the retroperitoneal space, and the detection of coeliomesenteric adenopathies, or possible lesions in the liver, spleen, and kidneys. The surveillance of most patients during treatment is possible with ultrasonography, if marked lipiodol resorption has occurred. Though this procedure is easy to conduct in all radiological departments, it does not have the same sensitivity as lymphography associated with computed tomography.

[Comparative study of 3 markers in ovarian cancer: CA 125, CA 19,9 and CEA]. / Etude comparative de trois marqueurs dans le cancer de l'ovaire: CA 125, CA 19,9 et ACE.

CA 125 is today the best tumour marker to follow up the evolution of epithelial cancers of the ovary where it is elevated in about 80% of cases (as compared with a positive finding in only 20% for CEA and CA 19,9): it is no use as a screening test, it does reflect the quality of the first debulking operation, it makes it possible to follow the clinical evolution of the disease and thus to modify the adjuvant treatment, it helps to indicate whether a second look operation should be carried out; but it does not dispense altogether with the second look operation because even when CA 125 returns to normal the disease is sometimes still not eradicated, finally, it gives an opportunity to look early for any recurrences.

[Adriamycin in low weekly doses. Latest therapy of advanced cancer of the breast]. / L'adriamycine à faible dose hebdomadaire. Dernière thérapeutique du cancer du sein avancé.

Thirty-four patients with heavily pretreated advanced breast cancer received adriamycin in weekly doses of 12 mg/m2. Twenty-two patients (18 assessable) had a performance status greater than or equal to 3 (WHO scale). There were 5 (28%) partial responses, 7 (39%) minimal responses, 3 cases (17%) with no change and 3 (17%) with progressive disease; the mean duration of response was superior to 9 months (range: 3-12 months). In the remaining 12 patients, who had resisted a previous multidrug regimen containing adriamycin, there were 3 (25%) partial responses, 2 (17%) minimal responses, 4 cases (33%) with no change and 3 (25%) with progressive disease; the mean duration of response was superior to 5 months (range: 3-11 months). More than 600 weekly injections were administered with only minor blood and digestive tract toxicities. No alopecia was recorded. The total cumulative dose of adriamycin was superior to 900 mg/m2 in 8 patients; none had clinically evident cardiac toxicity. Adriamycin extravasation with subsequent tissue necrosis occurred on 10 occasions due to the frequency of administration; this problem was solved by the systematic installation of central venous catheters.

[Conservative treatment of cancer of the breast. Apropos of 108 cases]. / Traitement conservateur du cancer du sein. A propos de 108 cas.

Between 1975 and 1980, 108 cancers of the breast (T1 and small T2) were treated by associated conservative surgery and radiotherapy. Axillary glands were curetted in 92 patients; 17% showed lymph node invasion. Radiotherapy was by telecobalt: 45 grays to the whole breast and 60 grays to the tumor bed. Esthetic results were satisfactory. Intramammary recurrence was rare (6%) and was independent of site or size of tumor and of degree of lymph node involvement. Metastases not associated with local recurrence were very rarely observed (4% of cases) and were present only in patients without glandular involvement. The 5-year actuarial survival rate was 95%.

Conservative treatment (chemotherapy/radiotherapy) of locally advanced breast cancer.

Once treated almost exclusively by radical surgery, locally advanced breast cancers (Stages III, IV; MO) were later treated solely by irradiation, but local results (cosmesis and recurrences) remained poor. Since 1977, we have used induction chemotherapy in an attempt to treat subclinical metastatic disease while allowing better quality mammary conservation in a greater number of patients. From 1977 to 1980, 25 patients (Stages III, IV; MO) were treated by a sequential association of chemotherapy (Adriamycin [doxorubicin], vincristine, cyclophosphamide, 5-fluorouracil; 3 cycles) followed by irradiation (45 Gy to the breast and nodal areas; 15-30 Gy mammary boost dose). Responses of 50% or more were observed in 86% of the breast lesions and in 80% of nodal lesions. This sequential treatment was always well tolerated. Local recurrences occurred in six patients (24%) who underwent mastectomy without any complications. The survival rate at 4 years is 55%.

An improved method for routine analysis of polyamines in biological fluids with a conventional amino acid analyzer.

An accurate and precise mechanized ion-exchange chromatographic method for the estimation of polyamines in biological fluids is described. The method includes the recent improvements developed for ion-exchange analysis of polyamines: the use of sulfonated polystyrene cation-exchange resin with a bead diameter of less than 10 micrometers and a continuous fluorescent detection with o-phthalaldehyde. Four different procedures for the removal of protein before analysis of polyamines in plasma have been compared. Linearity of the fluorescence detection, reproducibility (intra, inter assay) and precision of the retention times are reported. Furthermore, the method is characterised by the simplicity of the sample preparation, a clear and rapid elution programme and especially by its routine applicability, as shown during the last six months in the Centre Antoine-Lacassagne.

Simultaneous micro measurement of steroid receptors in breast cancer.

The oestradiol (RE) and progesterone (RP) receptor levels were analyzed in 26 tumour fragments (200-500 mg) from breast cancer patients. After pulverization of tissue, one part was analyzed by the routine dextran-coated charcoal (DCC) method and the other by a micromethod as follows: (i) cytosol incubation using the DCC method but in the simultaneous presence of [3H]oestradiol and [3H]R5020 (ii) extraction of the steroids bound to the receptor by precipitation with ethanol/TCA (iii) high pressure liquid chromatography (HPLC) on a modular system, with a C185 microns column and an elution by gradient mixture methanol/water. The fractions were collected and the radioactivity counted. The separation of oestradiol from R 5020 was rapid and complete. In addition dexamethasone was separated by this system making possible triple measures of RE, RP and glucocorticoid receptors. A highly significant correlation was obtained between the 2 methods: RE = 0.996, P less than 0.001; RP r = 0.975, P less than 0.001, implying that the thresholds of positivity, i.e. for therapeutic decisions, remain unchanged. Simultaneous measurement of RE and RP in a single needle biopsy is possible with this micromethod.

[Polyamines and malignant diseases (author's transl)]. / Polyamines et affections malignes.

The aliphatic polyamines (putrescine, spermidine, spermine) are associated with the phenomena of normal and neoplastic cellular growth. Two third of cancers generally show elevated urinary excretion of polyamines. The urinary levels of polyamines are significantly higher in cancer in evolution than in cancer in remission. The variable association of polyamines with different localisations is reviewed. The potential interest of polyamines analysis in the diagnosis and prognosis of cancer is discussed. The more exciting application of this test remains in the possibility of a short term appreciation of the oncostatic treatment efficiency.

The clinical value of urinary polyamine analyses in cancer patients.

The polyamines, putrescine (P) and spermidine (S), have been measured in 185 cancer patients. Patients in remission exhibited significantly different levels from those with active disease. In a dynamic patient study, followed over a period of 5-6 months, the urinary polyamine levels correlated closely with the clinical status. Furthermore, polyamines have been measured 24 h before beginning chemotherapy (P1, S1) and 48 h after its onset (P2, S2). The value of the ratio, (S2/P2)/(S1/P1), was found to correlate with the type of response to chemotherapy.